Bioabsorbable polymeric compositions, processing methods, and medical devices therefrom

ABSTRACT

Novel bioabsorbable polymeric blends are disclosed. The blends have a first component that is a polylactide polymer or a copolymer of lactide and glycolide and a second component that is poly(p-dioxanone) polymer. The novel polymeric blends provide medical devices having dimensional stability. Also disclosed are novel bioabsorbable medical devices made from these novel polymer blends, as well as novel methods of manufacture.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of pending U.S. application Ser. No.12/887,995 filed Sep. 22, 2010, the entire disclosures of which arehereby incorporated in their entirety.

FIELD OF THE INVENTION

The field of art to which this invention relates is bioabsorbablepolymers, in particular, bioabsorbable polymer blends useful formanufacturing medical devices.

BACKGROUND OF THE INVENTION

Bioabsorbable polymers and medical devices made from such polymers areknown in the art. Conventional bioabsorbable polymers include polylacticacid, poly(p-dioxanone), polyglycolic acid, copolymers of lactide,glycolide, p-dioxanone, trimethylene carbonate, ε-caprolactone, invarious combinations, etc. The bioabsorbable polymers are designed tohave a chemistry such that the polymers breakdown in vivo and are eithermetabolized or otherwise broken down, for example by hydrolysis, andexcreted from the patient's body. The advantages of utilizingimplantable medical devices made from bioabsorbable polymers arenumerous and include, for example, eliminating the need for additionalsurgeries to remove an implant after it serves its function. Ideallywhen a “temporary presence” of the implant is desired, support can beprovided until the tissue heals.

The bioabsorbable polymers used to manufacture medical devices have beenon occasion polymeric blends of absorbable polymers and copolymersengineered to provide specific characteristics and properties to themanufactured medical device, including bioabsorption rates, breakingstrength retention, and dimensional stability, etc.

There are many conventional processes used to manufacture medicaldevices from bioabsorbable polymers and polymer blends. The processesinclude injection molding, solvent casting, extrusion, machining,cutting and various combinations and equivalents. A particularly usefuland common manufacturing method is thermal forming using conventionalinjection molding processes. It is known in this art that manufacturingprocesses such as thermal injection molding may result in molded partsthat have inferior properties, especially, for example, unacceptabledimensional stability, mechanical properties, and retention ofmechanical properties with time post-implantation. There are a number ofreasons for diminished dimensional stability. They include the presenceof residual stresses induced during the manufacturing process. Anotherreason is if at least one of the polymeric components possesses too lowa glass transition temperature, especially if the polymeric componentdoes not easily crystallize after molding.

Therefore, there is a need in this art for novel bioabsorbable polymerblends that can be used in thermal injection molding processes, andother conventional processes, to manufacture bioabsorbable medicaldevices having superior breaking strength retention, excellentbioabsorption, superior mechanical properties such as stiffness andstrength, manufacturability, and superior dimensional stability.

It is known when using thermal injection molding processes that processconditions and design elements that reduce shear stress during cavityfilling will typically help to reduce flow-induced residual stress.Likewise, those conditions that promote sufficient packing and uniformmold cooling will also typically tend to reduce thermally-inducedresidual stress. It is often very difficult, if not nearly impossible,to completely eliminate residual stress in injection molded parts.Approaches that have been employed include: (1) attempting tocrystallize the part while still in the mold to increase the mechanicalrigidity to resist distortion; and, (2) employing resins having a highglass transition temperature (T_(g)).

This later case describes the situation wherein chain mobility is onlyreached at much higher temperatures, thus protecting the part at themoderate temperatures that the part might be expected to endure duringethylene oxide (EO) sterilization, shipping, and storage. Materialspossessing high glass transition temperatures may not necessarilypossess other characteristics that are desirable such as absorbability.Residual stresses are believed to be the main cause of part shrinkageand warpage. Parts may warp or distort dimensionally upon ejection fromthe mold during the injection molding cycle, or upon exposure toelevated temperatures, encountered during normal storage or shipping ofthe product.

There have been attempts in the prior art to address the problem of lackof dimensional stability in medical devices thermally formed from meltblended bioabsorbable polymers. Smith, U.S. Pat. No. 4,646,741,discloses a melt blend of a lactide/glycolide copolymer andpoly(p-dioxanone) used to make surgical clips and two-piece staples. Themelt blends of Smith provide molded articles possessing dimensionalstability; Smith requires that the amount of poly(p-dioxanone) in theblend is greater than 25 weight percent and teaches away from loweramounts. The polymer blends of Smith have disadvantages associated withtheir use to manufacture medical devices, including: limited stiffnessor Young's modulus, shorter retention of mechanical properties uponimplantation, greater sensitivity to moisture limiting the allowableopen storage time during manufacture, and, although difficult toquantify, more difficult thermal processing.

As mentioned previously, residual stresses are believed to be the maincause of part shrinkage and warpage. It is known that flow-inducedresidual stresses may have an effect upon a thermally molded polymericmedical device. Unstressed, long-chain polymer molecules tend to conformto a random-coil state of equilibrium at temperatures higher than themelt temperature (i.e., in a molten state). During thermal processing(e.g. injection molding), the molecules orient in the direction of flow,as the polymer is sheared and elongated. Solidification usually occursbefore the polymer molecules are fully relaxed to their state ofequilibrium and some molecular orientation is then locked within themolded part. This type of frozen-in, stressed state is often referred toas flow-induced residual stress. Anisotropic, non-uniform shrinkage andmechanical properties in the directions parallel and perpendicular tothe direction of flow are introduced because of the stretched molecularstructure.

Cooling can also result in residual stresses. For example, variation inthe cooling rate from the mold wall to its center can causethermally-induced residual stress. Furthermore, asymmetricalthermally-induced residual stress can occur if the cooling rate of thetwo surfaces is unbalanced. Such unbalanced cooling will result in anasymmetric tension-compression pattern across the part, causing abending moment that tends to cause part warpage. Consequently, partswith non-uniform thickness or poorly cooled areas are prone tounbalanced cooling, and thus to residual thermal stresses. Formoderately complex parts, the thermally-induced residual stressdistribution is further complicated by non-uniform wall thickness, moldcooling, and mold constraints.

It should be noted that a common, conventional method of sterilizationis exposure to ethylene oxide gas in a sterilization process cycle.Absorbable polymeric devices are frequently sterilized by exposure toethylene oxide (EO) gas. EO can act as a plasticizer oflactide-glycolide copolymers, and can lower the T_(g) slightly; this mayresult in ‘shrinkage’ and/or ‘warpage’ of an injection-molded part,especially when exposed to temperatures higher than the Tg. This addsadditional processing and handling challenges when usinglactide-glycolide polymeric materials for absorbable medical devices. Itshould be noted that the EO sterilization process not only exposes thepart to EO gas, it also exposes the part to elevated temperatures. Thisusually requires treatment at slightly elevated temperatures. Because EOcan act as a plasticizer of synthetic absorbable polyesters, theproblems of shrinkage and warpage and general dimensional instabilityare often exacerbated.

There are a number of processing methods conventionally used to reduceor eliminate shear stresses during processing. Process conditions anddesign elements that reduce shear stress during cavity filling will helpto reduce flow-induced residual stress. Polymeric parts are often heattreated (thermally annealed) to alter their performance characteristics.The reason for the heat treatment processing is to mature themorphological development, for example crystallization and/or stressrelaxation. If done successfully, the resulting part may exhibit betterdimensional stability and may exhibit better mechanical strength.

Injection molded parts ejected from the injection molding machine thatare not already distorted, can be cooled/quenched to room temperatureand may appear to be dimensionally sound. Stresses, however, are usuallystill present and can drive distortion any time the polymer chains areallowed to mobilize. As previously described, this can happen with anincrease in temperature or exposure to a plasticizer such as EO gas. Inorder to overcome this potential driving force for dimensionaldistortion, a number of strategies have been taken; these include(thermal) annealing.

If the part can be dimensionally constrained, thermal annealing can beemployed towards two goals: one is to attempt to reduce the amount ofmolecular orientation in the polymer chains, also known as stressreduction; and, another is to increase the crystallinity in the part toincrease the mechanical rigidity to resist distortion.

With some polymers that readily crystallize, one might be able tocrystallize the part while it is still in the mold, but this is anunusual situation. Here the mold cavity not only acts to define theshape of the part, it can act to restrain the shape of the part duringthe crystallization process. With more-difficult-to-crystallizepolymers, the cycle time becomes prohibitively long, and the injectionmolding process becomes impractical. Thus, the part needs to be ejectedfrom the mold before complete polymer morphology development takesplace.

Injection molded parts prepared from semi-crystalline polymers can oftenbe annealed by thermal treatment to increase crystallinity level andcomplete their polymer morphology development. Often the parts must bephysically constrained to avoid the distortion one is attempting toavoid. Once crystallized, the part has increased mechanical rigidity toresist distortion if exposed to normally distorting conditions.Providing suitable physical constraint is often difficult, as it isoften labor intensive and economically taxing.

Annealing the ejected part without need for physical constraint ispreferred; however what often happens is that the part distorts duringthe annealing process rendering the part unacceptable for many needs.

It is known in the industry to anneal parts to reduce molded-in-stressesby thermal relaxation. The time and temperature required to relievestress varies but must often be done below the T_(g) to avoid grossdistortion. Even then the results can vary greatly. It is more difficultto reduce stress levels, without causing distortion, in higher molecularweight resins. It would be relatively easy to reduce molded-in-stressesby thermal relaxation in low molecular weight, high flow, polyesters, ascompared to higher molecular weight polyesters.

Regarding the molecular weight of the polymer blend, higher molecularweight usually develops higher stress levels and requires longertimes/higher temperatures for stress relaxation. Although this is thecase, higher molecular weight is often needed to achieve high mechanicalproperties and biological performance. This situation often presents aproblem for the device manufacturer.

In order to impart more crystallinity to increase mechanical rigidity tobetter resist distortion, or to reduce molecular orientation in order tolower the driving force for distortion, the parts would ideally beprocessed by thermal treatment (annealing) at a temperature which doesnot cause distortion. Unfortunately, due to the nature of the syntheticabsorbable polyesters commonly employed, this treatment often needs tobe above their glass transition temperature where distortion is nearlyimpossible to avoid.

Consider for example, polylactide homopolymeric orpoly(lactide-co-glycolide)copolymeric devices. The stressed polymerchains of these injection-molded parts will tend to relax and return totheir natural state (“random three-dimensional coils”) when heated to orabove their glass transition temperatures. This will be observed aswarpage, shrinkage or general dimensional deformation. It is a generalpractice in the industry when producing molded polylactide-based parts,not to anneal them because of this potential deformation. Theseas-molded polylactide parts are of very low crystallinity, if notoutright amorphous or non-crystalline, and will then tend to deform ifexposed to temperatures at or above their respective glass transitiontemperatures. It would be advantageous to be able to anneal such partsto induce crystallinity so that they may develop the high rigidity toremain dimensionally stable under conditions normally encountered duringEO sterilization, shipping, and storage.

There are medical applications that require the medical device todisplay sufficient column strength such as in the case of an implantablestaple or a tack. Clearly, for a device having such a requirement with asmaller cross-sectional area, the polymer from which it was formed mustbe inherently stiff if the tack is to function properly for the intendedapplication.

To achieve higher stiffness in a melt blend of a lactide/glycolidecopolymer and poly(p-dioxanone), one needs to minimize the amount ofpoly(p-dioxanone). Contrary to what Smith teaches, it has been foundthat dimensional stability can be achieved in parts molded from a blendof a lactide-rich copolymer and poly(p-dioxanone), in which the levelsof poly(p-dioxanone) are lower than 25 weight percent. The addition ofthe poly(p-dioxanone), even at these low levels, enhances the ability toachieve dimensional stability in the final part.

Even though such polymer blends are known, there is a continuing need inthis art for novel absorbable polymeric materials that provide a medicaldevice with improved characteristics including stiffness, retainedstrength in vivo (in situ), dimensional stability, absorbability invivo, and manufacturability, along with a need for novel medical devicesmade from such polymeric materials, and novel methods of manufacturingmedical devices from such polymeric materials.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel bioabsorbablepolymer blends that can be used in manufacturing processes to producenovel absorbable medical devices and medical device components by meltprocesses, such as injection molding, and by other processes, whereinthe devices or components have superior mechanical properties (such ashigh stiffness and column strength), superior breaking strengthretention, acceptable bioabsorption rates, and superior dimensionalstability.

Accordingly, a novel bioabsorbable polymer blend composition isdisclosed. The polymer blend has a first bioabsorbable polymer and asecond bioabsorbable polymer. The first polymer contains about 76 weightpercent to about 92 weight percent of a lactide-rich polymer containingabout 100 mol percent to about 70 mol percent of polymerized lactide,and about 0 mol percent to about 30 mol percent of polymerizedglycolide. The second polymer is poly(p-dioxanone). The maximum weightpercent of poly(p-dioxanone) in the blend is about 24 weight percent andthe minimum weight percent of poly(p-dioxanone) in the blend dependsupon the molar amount of polymerized lactide in the lactide-richpolymer, and is calculated by the expression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)The polymer blend provides dimensional stability to a manufacturedarticle.

Another aspect of the present invention is a thermally processedbioabsorbable polymer blend composition. The polymer blend has a firstbioabsorbable polymer and a second bioabsorbable polymer. The firstpolymer contains about 76 weight percent to about 92 weight percent of alactide-rich polymer containing about 100 mol percent to about 70 molpercent of polymerized lactide and about 0 mol percent to about 30 molpercent of polymerized glycolide. The second polymer ispoly(p-dioxanone). The maximum weight percent of poly(p-dioxanone) inthe blend is about 24 weight percent and the minimum weight percent ofpoly(p-dioxanone) in the blend depends upon the molar amount ofpolymerized lactide in the lactide-rich polymer and is calculated by theexpression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)The thermally processed polymer blend provides dimensional stability toa manufactured article.

Yet another aspect of the present invention is a novel bioabsorbablemedical device. The medical device has a structure. The medical devicecomprises a bioabsorbable polymer blend of a first bioabsorbable polymerand a second bioabsorbable polymer. The first polymer contains about 76weight percent to about 92 weight percent of a lactide-rich polymercontaining about 100 mol percent to about 70 mol percent polymerizedlactide and about 0 mol percent to about 30 mol percent polymerizedglycolide. The second polymer is poly(p-dioxanone). The maximum weightpercent of poly(p-dioxanone) in the blend is about 24 weight percent andthe minimum weight percent of poly(p-dioxanone) in the blend dependsupon the molar amount of polymerized lactide in the lactide-rich polymerand is calculated by the expression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)The polymer blend provides dimensional stability to the medical device.

Still yet another aspect of the present invention is a method ofmanufacturing a medical device. The method includes the steps ofprocessing a bioabsorbable polymer blend. The polymer blend has a firstbioabsorbable polymer and a second bioabsorbable polymer. The firstpolymer contains about 76 weight percent to about 92 weight percent of alactide-rich polymer containing about 100 mol percent to about 70 molpercent of polymerized lactide and about 0 mol percent to about 30 molpercent of polymerized glycolide. The second polymer ispoly(p-dioxanone). The maximum weight percent of poly(p-dioxanone) inthe blend is about 24 weight percent and the minimum weight percent ofpoly(p-dioxanone) in the blend depends upon the molar amount ofpolymerized lactide in the lactide-rich polymer and is calculated by theexpression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)A bioabsorbable medical device is formed from the polymer blend. Thepolymer blend provides dimensional stability to the formed medicaldevice.

Further aspects of the present invention include the above-describedmedical device and method, wherein the polymer blend is thermallyprocessed.

These and other aspects and advantages of the present invention willbecome more apparent from the following description and accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a SEM photomicrograph of the collected poly(p-dioxanone)structures of the injection molded articles from the polymer blend of 20weight percent poly(p-dioxanone) and 80 weight percentpoly(lactide-co-glycolide), wherein the poly(lactide-co-lactide) is 85mol percent polymerized lactide and 15 mol percent polymerizedglycolide.

FIG. 2 is a drawing of an implantable staple or tack demonstrating thepresent invention, and shows a device with a small cross-sectional area.

FIG. 3 is a drawing of the device of FIG. 2 showing critical dimensionsof said device.

FIG. 4 is a graph showing the effects of compositional changes of theinjection molded device, as related to breaking strength retention orBSR, after being subjected to in-vitro testing.

FIG. 5 is a graph of mol percent polymerized lactide in thelactide/glycolide copolymer component versus weight percent ofpoly(p-dioxanone); the area bounded by the curves contains the novelpolymer compositions of the present invention.

FIG. 6a is a photograph of an injection molded tack of EXAMPLE 8C (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6C thatprovided injection molded tacks exhibiting unacceptable warping afterannealing.

FIG. 6b is a photograph of an injection molded tack of EXAMPLE 9C(similar to the tack of FIG. 6a , but after annealing) made from thepolymer composition of EXAMPLE 6C that provided injection molded tacksexhibiting unacceptable warping after annealing.

FIG. 7a is a photograph of an injection molded tack of EXAMPLE 8D (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6D thatprovided injection molded tacks that exhibit superior dimensionalstability and an acceptable level of warping after annealing.

FIG. 7b is a photograph of an injection molded tack of EXAMPLE 9D(similar to the tack of FIG. 7a , but after annealing) made from thepolymer composition of EXAMPLE 6D that provides injection molded tacksthat exhibit superior dimensional stability and an acceptable level ofwarping after annealing.

FIG. 8a is a photograph of an injection molded tack of EXAMPLE 8N (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6N thatprovided injection molded tacks that exhibit superior dimensionalstability and an acceptable level of warping after annealing.

FIG. 8b is a photograph of an injection molded tack of EXAMPLE 9N(similar to the tack of FIG. 8a , but after annealing) made from thepolymer composition of EXAMPLE 6N that provided injection moldedarticles that exhibit superior dimensional stability and an acceptablelevel of warping after annealing.

FIG. 9a is a photograph of an injection molded tack of EXAMPLE 8S (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6S thatprovided injection molded tacks that exhibit unacceptable warping afterannealing.

FIG. 9b is a photograph of an injection molded tack of EXAMPLE 9S(similar to the tack of FIG. 9a , but after annealing) made from thepolymer composition of EXAMPLE 6S, that provided injection molded tacksthat exhibit unacceptable warping after annealing.

FIG. 10a is a photograph of an injection molded tack of EXAMPLE 8T(i.e., prior to annealing) made from the polymer composition of EXAMPLE6T that provided injection molded tacks that exhibit superiordimensional stability and an acceptable level of warping afterannealing.

FIG. 10b is a photograph of an injection molded tack of EXAMPLE 9T(similar to the tack of FIG. 10a , but after annealing) made from thepolymer composition of EXAMPLE 6T that provided injection molded tacksthat exhibit superior dimensional stability and an acceptable level ofwarping after annealing.

FIG. 11a is a photograph of an injection molded tack of EXAMPLE 8X(i.e., prior to annealing) made from the polymer composition of EXAMPLE6X that provided injection molded tacks that exhibit superiordimensional stability and an acceptable level of warping afterannealing.

FIG. 11b is a photograph of an injection molded tack of EXAMPLE 9X(similar to the tack of FIG. 11a , but after annealing) made from thepolymer composition of EXAMPLE 6X that provided injection molded tacksthat exhibit superior dimensional stability and an acceptable level ofwarping after annealing.

FIG. 12 is a drawing of a dumbbell test article.

DETAILED DESCRIPTION OF THE INVENTION

The novel polymer blends of the present invention are made frombioabsorbable polyester polymers and copolymers. Preferably, one of theblend components is either poly(L(−)-lactide), or a lactide-richlactide/glycolide copolymer. Another blend component is thebioabsorbable polymer poly(p-dioxanone).

The poly(L(−)-lactide), or a lactide-rich lactide/glycolide copolymerwill be manufactured in a conventional manner. A preferred manufacturingmethod is as follows: the lactone monomers are charged along with analcohol initiator, a suitable catalyst, and dye if desired, into astirred pot reactor. After purging to remove oxygen, under a nitrogenatmosphere the reactants are heated with agitation to conduct a ringopening polymerization. After a suitable time the formed resin isdischarged and sized appropriately. The resin particles are subjected toa devolitalization process and are subsequently stored under vacuum. Themol percent of polymerized lactide and polymerized glycolide in thelactide-rich polymer useful in the novel blends of the present inventionmay be varied to provide desired characteristics. Typically, the molpercent of polymerized lactide in the lactide-rich polymer will be about70 percent to about 100 percent, more typically about 80 percent toabout 90 percent, and preferably about 83 percent to about 87 percent.When the polymerized lactide in the lactide-rich polymer is 100 percent,the polymer is polylactide; poly(L(−)-lactide) is preferred for somesurgical applications. Typically, the mol percent of polymerizedglycolide in the lactide-rich polymer will be about 0 percent to about30 percent, more typically about 10 percent to about 20 percent, andpreferably about 13 percent to about 17 percent.

The poly(L(−)-lactide) homopolymer, or a lactide-rich lactide/glycolidecopolymer is characterized by chemical analysis. These characteristicsinclude, but are not limited to, an inherent viscosity range from about0.80 to about 2.25 dL/g, as measured in hexafluoroisopropanol at 25° C.and at a concentration of 0.1 g/dL. Gel permeation chromatographyanalysis showed a weight average molecular weight range fromapproximately 35,000 to 120,000 Daltons. It is to be understood thathigher molecular weight resins can be employed provided the processingequipment used to form the blend, and to form the medical device, iscapable of handling the melt viscosities inherent to these highermolecular weights and may be desirable for certain applications. Forexample, in some applications, a resin with an inherent viscosity of 2.5dL/g may be needed to produce medical devices requiring certaincharacteristics, such as higher strength. Differential scanningcalorimetry showed a glass transition temperature range from 20 to 65°C. and a melting transition from approximately 120 to 180° C. Nuclearmagnetic resonance analysis confirmed that the copolymeric resin is arandom copolymer of L(−)-lactide and glycolide. X-ray diffractionanalysis showed a crystallinity level of approximately 20 to 45 percent.

It is to be understood that the polylactide homopolymer blend component,or a lactide-rich lactide/glycolide copolymer blend component can bebased on the lactide monomer of LL configuration, that is, L(−)-lactide.However, other stereo-chemical isomers can be substituted provided thatin the final device, the lactide based polymer component exhibits enoughcrystallinity to provide dimensional stability. Thus, the homopolymer,poly(D(+)-lactide) based on the DD configuration might be used insteadof poly(L(−)-lactide). A lactide/glycolide copolymer component might bebased entirely on the DD-isomer, or have mixtures of the DD-isomer andthe LL-isomer, provided the crystallinity requirement in the finaldevice is met. Meso-lactide, the DL-isomer might also be used in smallproportions, again provided the crystallinity requirement in the finaldevice is met.

The poly(p-dioxanone) polymer useful in the novel polymer blends of thepresent invention is manufactured in a conventional manner. A preferredmethod of manufacturing such polymer is as follows: the lactone monomeris charged along with an alcohol initiator, a suitable catalyst, and dyeif desired, into a stirred pot reactor. The dye should be one acceptablefor clinical use; these include D&C Violet No. 2 and D&C Blue No. 6.After purging to remove oxygen, the reactants are heated under anitrogen atmosphere with agitation to conduct a ring openingpolymerization. After a suitable time, the formed resin is dischargedinto appropriate containers, and further polymerized under conditionsknown as “solid state” polymerization. An alternative method may includepolymerization in the melt. After this reaction period is complete, thepolymer resin is sized appropriately. The resin particles are subjectedto a devolitalization process to remove unreacted monomer and aresubsequently stored under vacuum. The polydioxanone polymers useful inthe blends of the present invention will have an inherent viscosity ofat least about 0.80 dL/g as measured at 25° C. and at a concentration of0.1 g/dL. The polydioxanone polymers particularly useful in the blendsof the present invention will have the following characteristics: Thesecharacteristics shall include, but are not limited to: an inherentviscosity range from about 0.80 to about 2.30 dL/g, as measured inhexafluoroisopropanol at 25° C. and at a concentration of 0.1 g/dL. Gelpermeation chromatography analysis showed a weight average molecularweight range from approximately 35,000 to 120,000 Daltons. It is to beunderstood that higher molecular weight resins can be employed providedthe processing equipment used to form the blend, and to form the medicaldevice, is capable of handling the melt viscosities inherent to thesehigher molecular weights and may be desirable for certain applications.For example, in some applications, a resin with an inherent viscosity of2.5 dL/g may be needed to produce medical devices requiring certaincharacteristics, such as higher strength. Differential scanningcalorimetry showed a glass transition temperature range from −15 to −8°C. and a melting transition from approximately 100 to 107° C. Nuclearmagnetic resonance analysis confirmed that the resin is a homopolymer ofpoly(p-dioxanone), with a composition of approximately 98 percentpolymerized p-dioxanone, and approximately 0 to 2 percent p-dioxanonemonomer, as measured on a molar basis. X-ray diffraction analysistypically showed a crystallinity level of approximately 25 to 40percent, although levels of 55 percent or higher have been observed.

The novel polymer blends of the present invention having improveddimensional stability will typically contain a first bioabsorbablepolymer and a second bioabsorbable polymer, the first polymer containingabout 76 weight percent to about 92 weight percent of a lactide-richpolymer containing about 100 mol percent to about 70 mol percentpolymerized lactide and about 0 mol percent to about 30 mol percentpolymerized glycolide, and the second polymer containingpoly(p-dioxanone), wherein the maximum weight percent ofpoly(p-dioxanone) in the blend is about 24 and the minimum weightpercent of poly(p-dioxanone) in the blend depends upon the molar amountof polymerized lactide in the lactide-rich polymer and is calculated bythe expression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)

To be clear, the novel polymer blends of the present invention aretypically a blend of a lactide-rich lactide/glycolide copolymer or apolylactide homopolymer, and poly(p-dioxanone). For example, thelactide/glycolide copolymer can be poly(L(−)-lactide-co-glycolide)having a composition of 85 mol percent polymerized lactide and 15 molpercent polymerized glycolide. The maximum weight percent ofpoly(p-dioxanone) in the blend is about 24 and one can calculate theminimum weight percent of poly(p-dioxanone) in the blend depending uponthe molar amount of polymerized lactide in the lactide/glycolidecopolymer, using the above equation. Thus for the case of an 85/15 (molbasis) lactide/glycolide copolymer:Minimum Weight Percent Poly(p-dioxanone)=(215.6212/Mol PercentPolymerized Lactide)^(2.7027)=(215.6212/85)^(2.7027)=12.4 Weight PercentPoly(p-dioxanone)

Thus for the novel polymer blends of the present invention employing an85/15 (mol basis) lactide/glycolide copolymer, the poly(p-dioxanone)weight percent would range between about 12.4 and about 24.

The novel polymer blends of the present invention will more typicallycontain about 76 weight percent to about 84 weight percent of thelactide-rich polymer, and about 16 weight percent to about 24 weightpercent of the poly(p-dioxanone), wherein the lactide-rich polymercontains about 80 mol percent to about 90 mol percent of polymerizedlactide and from about 10 mol percent to about 20 mol percent ofpolymerized glycolide.

The novel polymer blends of the present invention will preferablycontain about 78 weight percent to about 82 weight percent of thelactide-rich polymer, and about 18 weight percent to about 22 weightpercent of the poly(p-dioxanone), wherein the lactide-rich polymercontains about 83 mol percent to about 87 mol percent of polymerizedlactide and from about 13 mol percent to about 17 mol percent ofpolymerized glycolide.

The blends of the present invention showed a crystallinity level of atleast about 15 percent, typically greater than about 25 percent, andmore preferably, greater than about 35 percent, as measured by x-raydiffraction.

The novel polymer blends of the present invention can be manufacturedfrom the individual components in a variety of conventional mannersusing conventional processing equipment. Examples of manufacturingprocesses include chemical reactions of the ring-opening andpolycondensation type, devolitilization and resin drying, dry blendingin a tumble dryer, solution blending, extrusion melt-blending, injectionmolding, thermal annealing, and ethylene oxide sterilization processes.An alternate to dry blending with subsequent melt blending of themixture could include the use of two or more feeders, preferablyloss-in-weight feeders, that supply the components to be blended to anextruder; the extruder can be of the single screw or twin screw variety.Alternately, multiple extruders can be used to feed melts of the blendcomponents, such as in co-extrusion.

The blends of the present invention may be made by thermal processes.Examples of thermal processes to produce the polymer blends of thepresent invention would be melt blending in an extruder which caninclude twin screw blending or single screw extrusion, co-extrusion,twin screw blending with simultaneous vented-screw vacuumdevolatilization, vacuum tumble drying with thermal devolitilization,monomer removal by solvent extraction at elevated temperature, and resinannealing.

The polymer components, as well as blends of the subject invention canbe sized by conventional means such as pelletization, granulation, andgrinding.

A further embodiment of the present invention would be feedingappropriately sized particles of the blend components directly to thehopper of the injection molding machine. It would be obvious to oneskilled in the art to apply this technique to other processingmethodologies, such as, but not limited to, film or fiber extrusion.Limiting the thermal history of the polymer blend components isadvantageous in that it avoids the possibility of premature degradation.Additional methods of thermal processing can include a process selectedfrom the group consisting of injection molding, compression molding,blow molding, blown film, thermoforming, film extrusion, fiberextrusion, sheet extrusion, profile extrusion, melt blown nonwovenextrusion, co-extrusion, tube extrusion, foaming, rotomolding,calendaring, and extrusion. As noted earlier, appropriately sizedparticles of the blend components can be blended in the melt using thesethermal processing means.

Although not wishing to be held to scientific theory, it is believedthat the morphological development in the final part is greatlyinfluenced by the device forming process, such as injection molding.Thus the melt blended resin may have a morphology with a very low aspectratio for the minor phase, poly(p-dioxanone). It may not be until thehigh shear device forming process (e.g., injection molding), that thehigh aspect ratio of the minor phase is realized.

Other examples of manufacturing process equipment include chemicalreactors ranging in size from two-gallon to seventy-five galloncapacity, process devolitilization dryers ranging from one cubic feet totwenty cubic feet, single and twin-screw extruders from about one inchto about three inches in diameter, and injection molders ranging fromabout seven to about 40 tons in size. A preferred method and associatedequipment for manufacturing the polymer blends of the present inventioncan be found in EXAMPLE 1 through EXAMPLE 6.

If desired, the polymer blends of the present invention may containother conventional components and agents. The other components,additives or agents will be present to provide additional effects to thepolymer blends and medical devices of the present invention includingantimicrobial characteristics, controlled drug elution,radio-opacification, and osseointegration.

Such other components will be present in a sufficient amount toeffectively provide for the desired effects or characteristics.Typically, the amount of the other adjuncts will be about 0.1 weightpercent to about 20 weight percent, more typically about 1 weightpercent to about 10 weight percent and preferably about 2 weight percentto about 5 weight percent.

Examples of antimicrobial agents include the polychloro phenoxy phenolssuch as 5-chloro-2-(2,4-dichlorophenoxy)phenol (also known asTriclosan).

Examples of radio-opacification agents include barium sulfate whileexamples of osseointegration agents include tricalcium phosphate.

The variety of therapeutic agents that can be used in the polymer blendsof the present invention is vast. In general, therapeutic agents whichmay be administered via pharmaceutical compositions of the inventioninclude, without limitation, antiinfectives, such as antibiotics andantiviral agents; analgesics and analgesic combinations; anorexics;antihelmintics; antiarthritics; antiasthmatic agents; adhesionpreventatives; anticonvulsants; antidepressants; antidiuretic agents;antidiarrheals; antihistamines; anti-inflammatory agents; antimigrainepreparations; contraceptives; antinauseants; antineoplastics;antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics,antispasmodics; anticholinergics; sympathomimetics; xanthinederivatives; cardiovascular preparations including calcium channelblockers and beta-blockers such as pindolol and antiarrhythmics;antihypertensives; diuretics; vasodilators, including general coronary,peripheral and cerebral; central nervous system stimulants; cough andcold preparations, including decongestants; hormones, such as estradioland other steroids, including corticosteroids; hypnotics;immunosuppressives; muscle relaxants; parasympatholytics;psychostimulants; sedatives; tranquilizers; naturally derived orgenetically engineered proteins, polysaccharides, glycoproteins, orlipoproteins; oligonucleotides, antibodies, antigens, cholinergics,chemotherapeutics, hemostatics, clot dissolving agents, radioactiveagents and cystostatics. Therapeutically effective dosages may bedetermined by in vitro or in vivo methods. For each particular additive,individual determinations may be made to determine the optimal dosagerequired. The determination of effective dosage levels to achieve thedesired result will be within the realm of one skilled in the art. Therelease rate of the additives may also be varied within the realm of oneskilled in the art to determine an advantageous profile, depending onthe therapeutic conditions to be treated.

Suitable glasses or ceramics include, but are not limited to phosphatessuch as hydroxyapatite, substituted apatites, tetracalcium phosphate,alpha- and beta-tricalcium phosphate, octacalcium phosphate, brushite,monetite, metaphosphates, pyrophosphates, phosphate glasses, carbonates,sulfates and oxides of calcium and magnesium, and combinations thereof.

Suitable polymers that may be included in the polymer blends of thepresent invention include: suitable biocompatible, biodegradablepolymers which may be synthetic or natural polymers. Suitable syntheticbiocompatible, biodegradable polymers include polymers selected from thegroup consisting of aliphatic polyesters, poly(amino acids),copoly(ether-esters), polyalkylenes oxalates, polyamides, tyrosinederived polycarbonates, poly(iminocarbonates), polyorthoesters,polyoxaesters, polyamidoesters, polyoxaesters containing amine groups,poly(anhydrides), polyphosphazenes, polydiglycolates, and combinationsthereof. It is to be understood that inclusion of additional suitablepolymers is dependent upon obtaining dimensional stability in thefabricated device.

For the purposes of this invention the above optional aliphaticpolyesters include, but are not limited to, homopolymers and copolymersof lactide (which include lactic acid, D-, L- and meso lactide),glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone(1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkylderivatives of trimethylene carbonate, and blends thereof.

Suitable natural polymers include, but are not limited to collagen,elastin, hyaluronic acid, laminin, gelatin, keratin, chondroitin sulfateand decellularized tissue.

Although not preferred, the medical devices of the present invention maycontain nonabsorbable polymers in addition to the absorbable polymerblends of the present invention. Examples of such devices may includebut are not limited to meshes, sutures, and staples, where theproperties of both the absorbable and nonabsorbable polymers areadvantageous.

Suitable nonabsorbable polymers include, but are not limited toacrylics; polyamide-imide (PAI); polyaryletherketones (PEEK);polycarbonates; thermoplastic polyolefins such as polyethylene (PE),polypropylene (PP), polymethylpentene (PMP), and polybutene-1 (PB-1);polyolefin elastomers (POE) such as polyisobutylene (PIB), ethylenepropylene rubber (EPR); polybutylene terephthalate (PBT); polyethyleneterephthalates (PET); polyamides (PA) such as nylon 6 and nylon 66;polyvinylidene fluoride (PVDF); polyvinylidenefluoride-co-hexafluropropylene (PVDF/HFP); polymethylmethacrylate (PMMA)and combinations thereof and equivalents.

The bioabsorbable medical devices of the present invention that are madefrom the polymer blends of the present invention include but are notlimited to conventional medical devices, especially implantable medicaldevices, including staples, tacks, clips, sutures, tissue fixationdevices, mesh fixation devices, anastomosis devices, suture and boneanchors, tissue and bone screws, bone plates, prostheses, supportstructures, tissue augmentation devices, tissue ligating devices,patches, substrates, meshes, tissue engineering scaffolds, drug deliverydevices, and stents.

An example of a medical device that can be molded from the polymerblends of the present invention is a tissue tack 10 as seen in FIG. 2.FIG. 2 is a drawing of an implantable staple or tack demonstrating thepresent invention, and shows a device with a small cross-sectional area.The material of this device must be inherently stiff if the tack is tofunction properly for the intended application.

The tack 10 is seen to have two leg members 20 connected by a connectingstrap member 30 at their proximal ends 22. The distal ends 26 are seento have barb members 50 extending distally therefrom. Barb members 50have distal tissue piercing points 60 and proximal barbs 70 havingpoints 72. Referring to FIG. 3, barb members 50 are seen to have alength 74 shown as dimension Y. The points 60 are seen to be spacedapart by a distance 76 shown as dimension X.

Suitable tacks that can be made from the polymer blends of the presentinvention are also disclosed and described in commonly-assigned U.S.patent application Ser. Nos. 12/464,143; 12/464,151; 12/464,165; and,12/464,177, which are incorporated by reference.

The ability of the injection molded articles to develop some level ofcrystallinity prior to annealing allows the parts to undergo anannealing cycle to further crystallize the poly(lactide-co-glycolide)phase of the blend without unduly warping or shrinking, that is whilemaintaining dimensional integrity.

Injection molded parts of the blends of the subject invention canadvantageously be subjected to an annealing cycle to mature the polymermorphology. This often increases the level of crystallinity in the part.This process helps to ensure that when the part is exposed to moderatelyelevated temperatures, especially when exposed to ethylene oxide duringsterilization, dimensional stability will be acceptable. Although notwanting to be held to scientific theory, it is believed that directlyafter injection molding, under many processing conditions, the articlesare almost completely amorphous, but when stored at room temperature thepoly(p-dioxanone) phase in the blend begins to crystallize. Polymericmaterials will only crystallize when stored at temperatures above theirglass transition temperature. The glass transition temperature ofpoly(p-dioxanone) is about minus 10° C., allowing the poly(p-dioxanone)to begin crystallizing during storage at room temperature. In someprocessing conditions, typically at longer holding times in the mold,the poly(p-dioxanone) component can crystallize. The ejected parts thenpossess a small amount of crystallinity due substantially to this phase.

The ability of the poly(p-dioxanone) phase in the blend to develop somelevel of crystallinity prior to annealing allows for the crystallizationof the poly(lactide-co-glycolide) phase without excessive distortion ofthe molded article. This is because the formation of an organized,semicrystalline, molecular structure increases the part's resistance todistortion at elevated temperatures. For instance, if an amorphous, 100%poly(lactide-co-glycolide) article were to be annealed, the part wouldlikely warp during the annealing process if there were even moderatestress levels present. The interdispersed, semicrystallinepoly(p-dioxanone) in the blend maintains the dimensional stability ofthe part during exposure to the elevated temperatures needed tocrystallize the poly(lactide-co-glycolide) phase of the blend. The endresult is a semicrystalline, dimensionally stable, injection moldedarticle.

The medical devices of the present invention can be thermally annealedat a temperature of at least 45 degrees centigrade for at least oneminute. More preferably, the medical devices of the present inventionare thermally annealed at a temperature of about 60 degrees centigradefor about 8 hours, followed by annealing at a temperature of about 70degrees centigrade for about 4 hours, followed by annealing at atemperature of about 80 degrees centigrade for about 4 hours.

The medical device of the present invention will exhibit a crystallinitylevel of at least about 15 percent, typically greater than about 25percent, and more preferably, greater than about 35 percent, as measuredby x-ray diffraction.

To further inhibit warping during the annealing process, the article mayalso be constrained mechanically by use of an annealing fixture.Speculatively, it may be possible to anneal the part fully confined, orconstrained. This would require the equivalent of annealing in the mold.This, of course, is often economically not feasible. However,constraining a limited number of dimensions during annealing may beeconomically possible. The articles in EXAMPLE 8 were annealed using anannealing fixture that supported the parts from distortion within thehorizontal plane of the part. Although this annealing fixture isintended to aid in the resistance of distortion at elevated temperaturesduring annealing, it will not prevent dimensionally unstable parts fromwarping.

As the lactide level in the poly(lactide-co-glycolide) portion of theblend decreases, crystallization of the poly(lactide-co-glycolide) phasebecomes more difficult. In blends using a poly(lactide-co-glycolide)copolymer less rich in polymerized lactide, an increased weight percentof poly(p-dioxanone) may be required to maintain dimensional stabilityof the molded article. Such copolymers include 70/30poly(lactide-co-glycolide).

As noted earlier, the greater the amount of molecular orientation, orstress, present in the formed medical device, the greater will be thedriving force to shrink or warp; shrinking and warping is usually viewedas a disadvantageous phenomena.

In the formation of devices using processing means that induce at leasta moderate level of molecular orientation, or stress, it would be anadvantage to maintain dimensional stability. One such fabricationmethodology that usually induces at least a moderate level of stress isinjection molding. To be clear, when forcing a molten polymer streamthrough a pathway that is narrow, and finally into a cavity, one usuallyencounters high shear rates and high stress levels. When this happens,the molecular chains tend to orient in the direction of the flow,thereby setting up the system for later shrinkage or warpage whensubjected to temperatures slightly elevated above the glass transitiontemperature, particularly during exposure to EO gas while sterilizing.

Evidence of a high shear forming process is the presence of highresidual stresses in the part; these can be measured in a variety ofways. One such way is by viewing a part through crossed-polarized films.Other ways of assessing residual stresses utilize Scanning ElectronMicroscopy (SEM) techniques. The phase architecture of the substantiallyimmiscible polymer blends of lactide/glycolide copolymers andpoly(p-dioxanone) further provide evidence of the level of stress thatthe blend was subjected to during processing. When in high shearsituations, usually the minor phase is non-spherical in nature. Theminor phase usually distorts to elongated ellipsoids with L/Ds greaterthan about 3 to worm-like structures having L/D values 50 or greater.The medical devices of the present invention will typically have aspectratios of the minor phase greater than about 3, more typically greaterthan about 5, and preferably greater than about 20. Depending on theshear field, one could envision non-circular cross-sections that aremore ribbon-like. When the minor phase is substantially spherical innature, one can conclude that: (1) the level of shear the polymer meltwas subjected to was quite low or (2) the processing conditions employedallowed the polymer melt to relax, and the subsequent elongated domainsreshaped to much lower L/D structures. In either case, the level ofresidual stress is expected to be low. A sphere-only minor phasemorphology may then be evidence of low residual stress.

Methods to ascertain phase architecture in immiscible polymer blendsinclude phase contrast microscopy (polarized light microscopy); atomicforce microscopy (AFM); electron microscopy including scanning,tunneling and transmission electron microscopy (SEM, STM, TEM). Othertechniques potentially include high resolution digital-opticalmicroscopy.

Sample preparation may be via cryogenic fracturing or by microtomingtechniques including cryogenic microtoming. Solvent etching has provento be a useful sample preparation methodology in a number of systems.

As would be known to one having ordinary skill in the art, in accessingthe morphology of the minor phase, it is important to realize that oneneeds to make measurements on the sample from different angularperspectives. Specifically, in parts having elongated features as mightbe found in the present article of this invention, an examinationlooking at only the cross-section may incorrectly indicate that theminor phase is spherical in nature. Only when assessed longitudinallywill it be revealed that the minor phase is actually elongated in naturewith a high aspect ratio.

The medical devices of the present invention will have an inherentviscosity of at least about 0.8 dL/g as measured inhexafluoroisopropanol at 25 degrees centigrade at a concentration of 0.1g/dL. Additionally, the inherent viscosity of the lactide-rich polymerwill be at least about 0.8 dL/g and the inherent viscosity of thepoly(p-dioxanone) will be at least about 0.8 dL/g, both as measured inhexafluoroisopropanol at 25 degrees centigrade at a concentration of 0.1g/dL.

The medical devices of the present invention will remain dimensionallystable when subjected to immersion in water at an elevated temperature.Preferably they will remain dimensionally stable when subjected toimmersion in water at 49 degrees centigrade. Most preferably, they willremain dimensionally stable when subjected to immersion in water at 70degrees centigrade.

In a preferred embodiment of the invention (EXAMPLE 7), the injectionmolded part is visible in the surgical field because the polymeric blendhas a violet colorant, or dye, interspersed throughout. This dye, D&CViolet #2, is introduced to the blend as part of the poly(p-dioxanone)homopolymer, which comprises from about 7 to about 24 weight percent ofthe blend. Alternatively, colorant may be introduced to the blend aspart of the lactide-based polymer. In yet another variation, the dye maybe added at the time the polymer components are blended together, suchas during a melt blending or dry blending process. It will be evident toone skilled in the art that the colorants may be added to the polymercompositions of the present invention in a variety of conventionalmanners in addition to the approaches described above. The colorants mayinclude D&C Violet No. 2 and D&C Blue No. 6, at amounts ranging fromabout 0.01 weight percent to about 0.3 weight percent of the polymerblend or medical device. For surgical applications where color is notneeded or desirable, undyed poly(p-dioxanone) homopolymer is used in theblend, so that the surgical article has no color.

The following examples are illustrative of the principles and practiceof the present invention, although not limited thereto.

EXAMPLE 1 Synthesis of Poly(L(−)-lactide)

Into a suitable 15-gallon stainless steel oil jacketed reactor equippedwith agitation, 25.0 kg of L(−)-lactide was added along with 58.77 g ofdodecanol and 4.38 mL of a 0.33M solution of stannous octoate intoluene. The reactor was closed and a purging cycle, along withagitation at a rotational speed of 12 RPM in an upward direction, wasinitiated. The reactor was evacuated to pressures less than 200 mTorrfollowed by the introduction of nitrogen gas. The cycle was repeatedseveral times to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The vessel was heated at arate of 180° C. per hour until the oil temperature reached approximately130° C. The vessel was held at 130° C. until the monomer was completelymelted and the batch temperature reached 110° C. At this point theagitation rotation was switched to the downward direction. When thebatch temperature reached 120° C., the agitator speed was reduced to 7.5RPM, and the vessel was heated using an oil temperature of approximately180° C., with a heat up rate of approximately 60° C. per hour. When themolten mass reached 178° C., the oil temperature was maintained atapproximately 180° C. for an additional period of 3 hours.

At the end of the reaction period, the agitator speed was reduced to 5RPM, the oil temperature was increased to 190° C., and the polymer wasdischarged from the vessel into suitable containers for subsequentannealing. The containers were introduced into a nitrogen annealing ovenset at 80° C. for a period of approximately 16 hours; during this stepthe nitrogen flow into the oven was maintained to reduce degradation dueto moisture.

Once this annealing cycle was completed, the polymer containers wereremoved from the oven and allowed to cool to room temperature. Thecrystallized polymer was removed from the containers and placed into afreezer set at approximately −20° C. for a minimum of 24 hours. Thepolymer was removed from the freezer and placed into a Cumberlandgranulator fitted with a sizing screen to reduce the polymer granules toapproximately 3/16 inches in size. The granules were then sieved toremove any “fines” and weighed. The net weight of the ground polymer was18.08 kg, which was then placed into a 3 cubic foot Patterson-Kelleytumble dryer.

The dryer was closed and the pressure was reduced to less than 200mTorr. Once the pressure was below 200 mTorr, dryer rotation wasactivated at a rotational speed of 5-10 RPM with no heat for 10 hours.After the 10 hour period, the oil temperature was set to 120° C. at aheat up rate of 120° C. per hour. The oil temperature was maintained atapproximately 120° C. for a period of 32 hours. At the end of thisheating period, the batch was allowed to cool for a period of 4 hours,while maintaining rotation and vacuum. The polymer was discharged fromthe dryer by pressurizing the vessel with nitrogen, opening thedischarge valve, and allowing the polymer granules to descend intowaiting vessels for long term storage.

The long term storage vessels were air tight and outfitted with valvesallowing for evacuation so that the resin was stored under vacuum. Theresin was characterized. It exhibited an inherent viscosity of 1.84dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 121,000Daltons. Differential scanning calorimetry revealed a glass transitiontemperature of 65° C. and a melting transition at 182° C. Nuclearmagnetic resonance analysis confirmed that the resin waspoly(L(−)-lactide) with a residual monomer content less than 1.0percent. X-Ray diffraction analysis showed a crystallinity level ofapproximately 64 percent.

EXAMPLE 2 Synthesis of 85/15 Poly(L(−)-lactide-co-glycolide)

Into a suitable 15-gallon stainless steel oil jacketed reactor equippedwith agitation, 43.778 kg of L(−)-lactide and 6.222 kg of glycolide wereadded along with 121.07 g of dodecanol and 9.02 mL of a 0.33M solutionof stannous octoate in toluene. The reactor was closed and a purgingcycle, along with agitation at a rotational speed of 12 RPM in an upwarddirection, was initiated. The reactor was evacuated to pressures lessthan 200 mTorr followed by the introduction of nitrogen gas. The cyclewas repeated several times to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The vessel was heated at arate of 180° C. per hour until the oil temperature reached approximately130° C. The vessel was held at 130° C. until the monomer was completelymelted and the batch temperature reached 110° C. At this point theagitation rotation was switched to the downward direction. When thebatch temperature reached 120° C., the agitator speed was reduced to 7.5RPM, and the vessel was heated using an oil temperature of approximately185° C., with a heat up rate of approximately 60° C. per hour, until themolten mass reached 180° C. The oil temperature was maintained atapproximately 185° C. for a period of 2.5 hours.

At the end of the reaction period, the agitator speed was reduced to 5RPM, the oil temperature was increased to 190° C., and the polymer wasdischarged from the vessel into suitable containers for subsequentannealing. The containers were introduced into a nitrogen annealing ovenset at 105° C. for a period of approximately 6 hours; during this stepthe nitrogen flow into the oven was maintained to reduce degradation dueto moisture.

Once this annealing cycle was complete, the polymer containers wereremoved from the oven and allowed to cool to room temperature. Thecrystallized polymer was removed from the containers and placed into afreezer set at approximately −20° C. for a minimum of 24 hours. Thepolymer was removed from the freezer and placed into a Cumberlandgranulator fitted with a sizing screen to reduce the polymer granules toapproximately 3/16 inches in size. The granules were then sieved toremove any “fines” and then weighed. The net weight of the groundpolymer was 39.46 kg, which was then placed into a 3 cubic footPatterson-Kelley tumble dryer.

The dryer was closed and the pressure is reduced to less than 200 mTorr.Once the pressure is below 200 mTorr, tumbler rotation was activated ata rotational speed of 8-15 RPM and the batch was vacuum conditioned fora period of 10 hours. After the 10 hour vacuum conditioning, the oiltemperature was set to a temperature of 120° C., for a period of 32hours. At the end of this heating period, the batch was allowed to coolfor a period of at least 4 hours, while maintaining rotation and highvacuum. The polymer was discharged from the dryer by pressurizing thevessel with nitrogen, opening the slide-gate, and allowing the polymergranules to descend into waiting vessels for long term storage.

The long term storage vessels were air tight and outfitted with valvesallowing for evacuation so that the resin is stored under vacuum. Theresin was characterized. It exhibited an inherent viscosity of 1.64dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 96,200Daltons. Differential scanning calorimetry revealed a glass transitiontemperature of 56° C. and a melting transition at 154° C. Nuclearmagnetic resonance analysis confirmed that the resin was a randomcopolymer of polymerized L(−)-lactide and glycolide, with a compositionof 83.1 percent polymerized L(−)-lactide, 15.2 percent polymerizedglycolide, 1.6 percent lactide monomer, and 0.1 percent glycolidemonomer, as measured on a molar basis. The total residual monomercontent was approximately 1.7 percent. X-ray diffraction analysis showeda crystallinity level of approximately 48 percent.

EXAMPLE 3 Synthesis of 75/25 Poly(L(−)-lactide-co-glycolide)

Into a suitable 15-gallon stainless steel oil-jacketed reactor equippedwith agitation, 19.709 kg of L(−)-lactide and 5.291 kg of glycolide wereadded along with 61.77 g of dodecanol and 4.60 mL of a 0.33M solution ofstannous octoate in toluene. The reactor was closed and a purging cycle,along with agitation at a rotational speed of 12 RPM in an upwarddirection, was initiated. The reactor was evacuated to pressures lessthan 200 mTorr followed by the introduction of nitrogen gas. The cyclewas repeated several times to ensure a dry atmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The vessel was heated at arate of 180° C. per hour until the oil temperature reached approximately130° C. The vessel was held at 130° C. until the monomer was completelymelted and the batch temperature reached 110° C. At this point theagitation rotation was switched to the downward direction. When thebatch temperature reached 120° C., the agitator speed was reduced to 7.5RPM, and the vessel was heated using an oil temperature of approximately185° C., with a heat up rate of approximately 60° C. per hour. Once themolten mass reached 180° C., the oil temperature was maintained at 185°C. for a period of 2.5 hours.

At the end of the reaction period, the agitator speed was reduced to 5RPM, the oil temperature was increased to 190° C., and the polymer wasdischarged from the vessel into suitable containers for subsequentannealing. The containers were introduced into a nitrogen annealing ovenset at 105° C. for a period of approximately 6 hours; during this stepthe nitrogen flow into the oven was maintained to reduce degradation dueto moisture.

Once this annealing cycle was completed, the polymer containers wereremoved from the oven and allowed to cool to room temperature. Thecrystallized polymer was removed from the containers and placed into afreezer set at approximately −20° C. for a minimum of 24 hours. Thepolymer was removed from the freezer and placed into a Cumberlandgranulator fitted with a sizing screen to reduce the polymer granules toapproximately 3/16 inches in size. The granules were then sieved toremove any “fines” and then weighed. The net weight of the groundpolymer was 17.89 kg, which was then placed into a 3 cubic footPatterson-Kelley tumble dryer.

The dryer was closed and the pressure was reduced to less than 200mTorr. Once the pressure was below 200 mTorr, tumbler rotation wasactivated at a rotational speed of 5-15 RPM and the polymer wasconditioned for 16 hours under vacuum with no heat. The dryertemperature was then set to 60-65° C. at a heat up rate of 100° C. perhour. The oil temperature was maintained at 60-65° C. for a period ofapproximately 9 hours. At the end of this heating period, the batch wasallowed to cool for a period of at least 4 hours, while maintainingrotation and high vacuum. The polymer was discharged from the dryer bypressurizing the vessel with nitrogen, opening the slide-gate, andallowing the polymer granules to descend into waiting vessels for longterm storage.

The long term storage vessels were air tight and outfitted with valvesallowing for evacuation so that the resin was stored under vacuum. Theresin was characterized. It exhibited an inherent viscosity of 1.56dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 102,000Daltons. Differential scanning calorimetry revealed a glass transitiontemperature of 48° C. and a melting transition at 132° C. Nuclearmagnetic resonance analysis confirmed that the resin was a randomcopolymer of polymerized L(−)-lactide and glycolide, with a compositionof 70.1 percent polymerized L(−)-lactide, 25.2 percent polymerizedglycolide, 4.5 percent lactide, and 0.2 percent glycolide, as measuredon a molar basis. The total residual monomer content was less than 5percent. X-ray diffraction analysis showed a crystallinity level ofapproximately 26 percent.

EXAMPLE 4 Synthesis of Poly(p-Dioxanone)

Into a suitable 65 gallon stainless steel oil-jacketed reactor equippedwith agitation, 164.211 kg of p-dioxanone monomer (PDO) was added alongwith 509 grams of dodecanol, 164 grams of D&C Violet #2 Dye, and 100grams of a 0.33M solution of stannous octoate in toluene. The reactorwas closed and a purging cycle, along with agitation at a rotationalspeed of 12 RPM in an upward direction, was initiated. The reactor wasevacuated to pressures less than 500 mTorr followed by the introductionof nitrogen gas. The cycle was repeated several times to ensure a dryatmosphere.

At the end of the final introduction of nitrogen, the pressure wasadjusted to be slightly above one atmosphere. The vessel was heated at arate of 180° C. per hour until the oil temperature reached approximately100° C. The vessel was held at 100° C. until the batch temperaturereached 50° C., at which point the agitator rotation was changed to thedownward direction. When the batch temperature reached 90° C., the oiltemperature was reset to 95° C. These conditions were maintained, andsamples were taken from the vessel to be measured for Brookfieldviscosity. When the polymer batch viscosity reached at least 110centipoise, the batch was ready for discharge. The agitator speed wasreduced to 5 RPM, and a pre-heated filter was attached to the vesseldischarge port. The polymer was discharged from the vessel into suitablecontainers, under a nitrogen purge, covered, and transferred into anitrogen curing oven set at 80° C. A solid state polymerization wasinitiated for a period of approximately 96 hours; during this step thenitrogen flow into the oven was maintained to minimize degradation dueto moisture.

Once the solid state curing cycle was complete, the polymer containerswere removed from the oven and allowed to cool to room temperature. Thecrystallized polymer was removed from the containers, and placed into afreezer set at approximately −20° C. for a minimum of 24 hours. Thepolymer was removed from the freezer and ground in a Cumberlandgranulator fitted with a sizing screen to reduce the polymer granules toapproximately 3/16 inches in size. The granules were then sieved toremove any “fines” and then placed into a 20 cubic foot Patterson-Kelleytumble dryer.

The dryer was closed and the pressure was reduced to less than 2 mmHg.Once the pressure was below 2 mmHg, dryer rotation was activated at arotational speed of 6 RPM with no heat for 10 hours. After the 10 hourperiod, the oil temperature was set to 95° C. at a heat up rate of 120°C. per hour. The oil temperature was maintained at 95° C. for a periodof 32 hours. At the end of this heating period, the batch was allowed tocool for a period of at least 4 hours, while maintaining rotation andvacuum. The polymer was discharged from the dryer by pressurizing thevessel with nitrogen, opening the discharge valve, and allowing thepolymer granules to descend into waiting vessels for long term storage.The storage vessels were air tight and outfitted with valves allowingfor evacuation so that the resin was stored under vacuum.

The resin was characterized. It exhibited an inherent viscosity of 1.99dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 85,000Daltons. Differential scanning calorimetry revealed a glass transitiontemperature of about −15° C. and a melting transition at about 105° C.Nuclear magnetic resonance analysis confirmed that the resin was thehomopolymer poly(p-dioxanone), with a residual monomer content less than2 percent. X-ray diffraction analysis showed a crystallinity level ofapproximately 40 percent. For polymers with a different target molecularweight, the initiator (dodecanol) can be adjusted to target the I.V.required. In addition, if the surgical application does not require anarticle with color, the addition of dye can be eliminated from theprocess steps, thereby producing a polymer that is “natural” or undyed.

EXAMPLE 5 Dry Blending

Once the lactide/glycolide and poly(p-dioxanone) polymers have beenproduced by the above described methods, appropriate amounts of thesecomponents, in divided form (ground) were combined in a dry blend. Thesedry blends are produced on a weight basis, depending on the particularapplication and surgical need. In the present example, poly(p-dioxanone)at 20 weight percent and a lactide/glycolide copolymer at 80 weightpercent, were dry blended.

In a clean 3-cubic foot Patterson-Kelley dryer, 36.0 kg of granules ofthe 85/15 molar lactide/glycolide copolymer of EXAMPLE 2 were weighedand added to the dryer. In the same 3-cubic foot dryer, 9.0 kg ofpoly(p-dioxanone) polymer granules of EXAMPLE 4 were weighed and addedto the dryer. The dryer was closed, and the vessel pressure was reducedto less than 200 MTorr. The rotation was started at 7.5 RPM andcontinued for a minimum period of one hour. The dry blend was thendischarged into portable vacuum storage containers, and these containerswere placed under vacuum, until ready for the next step.

For the purpose of this invention, blends of this type can be producedin a similar manner with different compositions. Other inventivecompositions that were made are summarized in Table I. Additionally,some blends of the prior art, specifically the Smith blends, were madefor comparative sake. Three blends that were made contained 30 weightpercent poly(p-dioxanone) and 70 weight percent of a lactide/glycolidecopolymer possessing 80, 85 and 90 mol percent polymerized L(−)-lactide,respectively. Again, for some demanding situations, these blendscontaining greater than about 24 weight percent of poly(p-dioxanone) aretoo soft.

EXAMPLE 6 Melt Blending

Once the dry blends have been produced and have been vacuum conditionedfor at least three days, the melt-blending step can begin. A ZSK-30twin-screw extruder was fitted with screws designed for melt blendingutilizing dual vacuum ports for purposes of volatilizing residualmonomer. The screw design contained several different types of elements,including conveying, compression, mixing and sealing elements. Theextruder was fitted with a three-hole die plate, and a chilled waterbath with water temperature set between 40 and 70° F. was placed nearthe extruder outlet. A strand pelletizer and pellet classifier wasplaced at the end of the water bath. The extruder temperature zones wereheated to a temperature of 160 to 180° C., and the vacuum cold trapswere set to −20° C. The pre-conditioned dry blend granules were removedfrom vacuum and placed in a twin-screw feed hopper under nitrogen purge.The extruder screws were set to a speed of 175-225 RPM, and the feederwas turned on, allowing the dry blend to be fed into the extruder.

The polymer melt blend was allowed to purge through the extruder untilthe feed was consistent, at which point the vacuum was applied to thetwo vacuum ports. The polymer blend extrudate strands were fed throughthe water bath and into the strand pelletizer. The pelletizer cut thestrands into appropriate sized pellets; it was found that pellets with adiameter of 1 mm and an approximate length of 3 mm suffice. The pelletswere then fed into the classifier. The classifier separated larger andsmaller pellets from the desired size, usually a weight of about 10-15mg per pellet. This process continued until the entire polymer dry blendwas melt blended in the extruder, and formed into substantially uniformpellets. Samples were taken throughout the extrusion process and weremeasured for polymer characteristics such as inherent viscosity,molecular weight and composition. Once the melt-blending process wascompleted, the pelletized polymer was placed in polyethylene bags,weighed, and stored in a freezer below −20° C. to await devolitilizationof residual monomer.

The polymer melt-blend was placed into a 3-cubic foot Patterson-Kelleydryer, which was placed under vacuum. The dryer was closed and thepressure was reduced to less than 200 mTorr. Once the pressure was below200 mTorr, dryer rotation was activated at a rotational speed of 10 RPMwith no heat for 6 hours. After the 6 hour period, the oil temperaturewas set to 85° C. at a heat up rate of 120° C. per hour. The oiltemperature was maintained at 85° C. for a period of 12 hours. At theend of this heating period, the batch was allowed to cool for a periodof at least 4 hours, while maintaining rotation and vacuum. The polymermelt-blend pellets were discharged from the dryer by pressurizing thevessel with nitrogen, opening the discharge valve, and allowing thepolymer pellets to descend into waiting vessels for long term storage.The storage vessels were air tight and outfitted with valves allowingfor evacuation so that the resin was storage under vacuum. The resin wascharacterized.

The dry-blend of EXAMPLE 5 was melt-blended by the above describedprocess. The resultant melt blend exhibited an inherent viscosity of1.70 dL/g, as measured in hexafluoroisopropanol at 25° C. and at aconcentration of 0.10 g/dL. Gel permeation chromatography analysisshowed a weight average molecular weight of approximately 88,000Daltons. Differential scanning calorimetry revealed two glass transitiontemperatures of about −15° C. and 55° C., and two melting transitiontemperatures at about 105 and 150° C. Nuclear magnetic resonanceanalysis confirmed that the resin was a blend of poly(p-dioxanone) and85/15 (mol percent) lactide/glycolide copolymer, with a composition ofapproximately 64 percent polymerized lactide, 24 percentpoly(p-dioxanone), and 11 percent polymerized glycolide, as measured ona molar basis. The total residual monomer content was less than 2percent. X-ray diffraction analysis showed a crystallinity level ofapproximately 40 percent.

As mentioned previously in EXAMPLE 5, blends of various compositionscomprising poly(p-dioxanone), polylactide homopolymers, and lactide-richlactide/glycolide co-polymers were produced by the above describedmethod. For the purposes of this invention, the polymers and melt-blendsoutlined below in Table I were produced using these methods. The polymerof EXAMPLES 1 and the melt blends of EXAMPLE 6 were injection moldedinto the surgical articles described in EXAMPLE 7, and were analyzed fortheir physical, biological and chemical characteristics.

TABLE I Melt Blends of Poly (p-dioxanone) and a Lactide-Rich,Lactide/Glycolide (Co)Polymer Blend Composition Based Mol Percent onWeight Percent Weight Percent Lactide in Poly(p-dioxanone)/ Poly(p- theL/G EXAMPLE L/G Copolymer dioxanone) Copolymer 6 A 0% Poly(p-dioxanone)/0.0 100.0 100% PLA 6 B 5% Poly(p-dioxanone)/ 5.0 100.0 95% PLA 6 C 7.5%Poly(p-dioxanone)/ 7.5 100.0 92.5% PLA 6 D 9% Poly(p-dioxanone)/ 9.0100.0 91% PLA 6 H 9% Poly(p-dioxanone)/ 9.0 90.0 91% 90/10 PLA/PGA 6 E10% Poly(p-dioxanone)/ 10.0 100.0 90% PLA 6 L 10% Poly(p-dioxanone)/10.0 85.0 90% 85/15 PLA/PGA 6 J 12% Poly(p-dioxanone)/ 12.0 90.0 88%90/10 PLA/PGA 6 P 13% Poly(p-dioxanone)/ 13.0 80.0 87% 80/20 PLA/PGA 6 K15% Poly(p-dioxanone)/ 15.0 90.0 85% 90/10 PLA/PGA 6 M 15%Poly(p-dioxanone)/ 15.0 85.0 85% 85/15 PLA/PGA 6 S 15%Poly(p-dioxanone)/ 15.0 75.0 85% 75/25 PLA/PGA 6 Q 17% poly(p-dioxanone)/ 17.0 80.0 83% 80/20 PLA/PGA 6 T 17.5% Poly(p-dioxanone)/17.5 75.0 82.5% 75/25 PLA/PGA 6 G 20% Poly(p-dioxanone)/ 20.0 95.0 80%95/5 PLA/PGA 6 N 20% Poly(p-dioxanone)/ 20.0 85.0 80% 85/15 PLA/PGA 6 R20% Poly(p-dioxanone)/ 20.0 80.0 80% 80/20 PLA/PGA 6 W 20%Poly(p-dioxanone)/ 20.0 75.0 80% 75/25 PLA/PGA 6 F 24%Poly(p-dioxanone)/ 24.0 100.0 76% PLA 6 X 24% Poly(p-dioxanone)/ 24.075.0 76% 75/25 PLA/PGA

EXAMPLE 7 Test Article Description

The article chosen for evaluation was a 5 mm laparoscopic device forhernia repair; it was in the form of a staple or strap with legs andtissue holding means to the end of the legs. The device is illustratedin FIG. 2. The article was geometrically complex and was sterilizedusing conventional ethylene oxide sterilization processes afterundergoing an annealing process. The device was used to fixateprosthetic mesh to soft tissue in both laparoscopic and open procedures.

EXAMPLE 8 Injection Molding

Injection molding is a process well known in the plastic industry. It isdesigned to produce parts of various shapes and sizes by melting theplastic, mixing and then injecting the molten resin into a suitablyshaped mold. After the resin is solidified, the part is generallyejected from the mold and the process continued.

For the purposes of this invention, a conventional 30-ton electricallycontrolled injection molding machine was used. The polymer of EXAMPLE 1and the polymer blends of EXAMPLE 6 were processed in the followinggeneral manner. The polymer and polymer blends were fed by gravity froma hopper, under nitrogen purge, into a heated barrel. The polymer wasmoved forward in the barrel by the screw-type plunger into a heatedchamber. As the screw advanced forward, the molten polymer and polymerblends were forced through a nozzle that rests against a mold, allowingthe polymer and polymer blends to enter a specially designed moldcavity, through a gate and runner system. The blend was formed into thepart in the mold cavity, and allowed to cool at a given temperature fora period of time. It was then removed from the mold, or ejected, andseparated from the gate and runner. The injection molding cycleconsisted of the entire series of events during the process. It beganwhen the mold closed, and was followed by the injection of the polymerand polymer blends into the mold cavity. Once the cavity was filled,hold pressure was maintained to compensate for material shrinkage. Next,the screw-plunger turned, feeding the next “shot” to the front of thescrew. The screw retracted as the next “shot” was prepared. The part wascooled in the mold to sufficient temperature, and the mold opened andthe part was ejected. The closing and ejection times lasted from afraction of a second to a few seconds. Cooling times were based on anumber of factors, including part size and material composition.

EXAMPLE 9 Annealing the Molded Part

Once the articles of EXAMPLE 8 were injection molded, they were thensubjected to an annealing cycle to mature the polymer morphology. Asnoted earlier, this often increases the level of crystallinity in thepart. The articles in EXAMPLE 8 were annealed using an annealing fixturethat supported the parts from distortion within the horizontal plane ofthe part. Although this annealing fixture is intended to aid in theresistance of distortion at elevated temperatures during annealing, itwill not prevent dimensionally unstable parts from warping.

The annealing cycle used for the articles in EXAMPLE 8 was composed ofthree steps: 60° C. for 8 hours, 70° C. for 4 hours, and then 80° C. for4 hours. The purpose of the 60° C. step is to further crystallize thepoly(p-dioxanone) phase in the blend before reaching the crystallizationtemperatures for the poly(lactide-co-glycolide) phase. The 70° C. stepbegins to crystallize the poly(lactide-co-glycolide) phase beforereaching the last step in the cycle. Finally, the 80° C. step furthercrystallizes the poly(lactide-co-glycolide) phase.

It should be noted that for a given device and given compositionannealing conditions may be found that optimize certain importantperformance characteristics. These advantageous annealing conditions canbe developed through experimentation, changing the annealing temperatureand annealing duration, and measuring the response.

EXAMPLE 10 Analytical Characterization of Molded Parts

In general, the molded parts were characterized for chemical compositionby Nuclear Magnetic Resonance (NMR); for molecular weight by inherentviscosity in hexafluoroisopropanol at 0.1 g/dL at 25° C., and/or gelpermeation chromatography (GPC); for morphology by X-ray diffraction,differential scanning calorimetry (DSC), and chemical etching. Analysiswas performed on parts prior to annealing, after annealing, and oftenafter EO sterilization.

Crystallinity levels of selected lots of the annealed injection moldedarticles can be found in the table below.

TABLE II Crystallinity Levels of Selected Lots of the Annealed InjectionMolded articles Molar Percent of Poly(p-dioxanone) Glycolide Content inPercent Crystallinity Weight Percent in the Lactide/Glycolide Level asMeasured the Blend Copolymer by X-Ray Diffraction 20 10 45.0 20 10 45.920 12 46.4 20 15 38.4 20 15 39.9 20 15 38.2 20 15 42.6 20 20 38.9 30 1536.3 30 20 45.6

EXAMPLE 11 In Vitro Testing; Mechanical Properties

Selected lots of the annealed injection molded articles of EXAMPLE 9were tested for their mechanical properties using an INSTRON tensiletesting machine, Model 5544 fitted with an appropriate load cell. Thearticles were placed in a fixture designed to grip the barbed legs onone end and the crown on the other. The force-to-break was recorded as“Zero-Day Breaking Strength”.

EXAMPLE 12 In Vitro Testing BSR Testing

Selected lots of the annealed injection molded articles of EXAMPLE 9were placed in containers filled with a suitable amount of phosphatebuffer at pH 7.27. The containers were then incubated at 37° C. and arepresentative sample size, typically ten, was retrieved periodicallyfor mechanical testing. The incubated articles were tested for theirmechanical properties using an INSTRON tensile testing machine in afashion similar to the method of EXAMPLE 11. The force-to-break wasrecorded as “Breaking Strength”. The ratio of “Breaking Strength” to“Zero-Day Breaking Strength” was calculated and reported as “BreakingStrength Retention” for each time period. The test results aregraphically presented in FIG. 4. FIG. 4 is a graph showing the effectsof compositional changes of the injection molded device, as related tobreaking strength retention or BSR, after being subjected to in-vitrotesting.

EXAMPLE 13 Penetration

The test articles of EXAMPLE 9N were tested for their ability topenetrate bodily tissue and affix surgical mesh. Using an INSTRONmachine, the force needed to affix a commercially available surgicalmesh to porcine big belly was measured. The penetration test utilizedcustom top and bottom fixtures. The top fixture was a seating fork topush the tack through the mesh, while the bottom fixture was a clamp tohold the porcine belly in place.

The test articles of Example 9N were found to function appropriately.That is to say that they displayed appropriate tip sharpness,dimensional stability, and had adequate stiffness and column strength.Depending on the functional need of the article, this stiffness may beincreased by decreasing the level of poly(p-dioxanone), such as fororthopedic applications. Likewise, the stiffness may be decreased byincreasing the level of poly(p-dioxanone), such as for soft tissueapplications.

EXAMPLE 14 Holding Strength

The ability to hold the surgical mesh to bodily tissue is an importantfunction, especially during the critical wound healing period. Theaffixed surgical mesh was subjected to mechanical forces to determinethe force required to disengage the mesh from the tissue; this force iscalled “Holding Strength”. More specifically, surgical mesh was affixedto porcine belly by inserting three articles from EXAMPLE 9N along oneside of the mesh. The mesh was then grasped with clamps attached to aforced gauge and pulled in a shear direction (parallel to the plane ofthe tissue) until the mesh disengaged from the tissue. The maximum forcewas recorded as the “Holding Strength”. Articles of EXAMPLE 9N generatedholding force values of about 10 to 11 pounds. Depending of the medicalapplication, the holding strength requirement will vary and thecomposition of the article utilized can be tailored to meet thatrequirement.

Holding strength data for articles made from blends of various weightaverage molecular weights at the 20 weight percent poly(p-dioxanone)/80weight percent 85/15 poly(L(−)-lactide-co-glycolide) composition wasobtained. The data is provided in Table III below:

TABLE III Holding Strength Data at Various Molecular Weights WeightAverage Molecular Weight (Da) Holding Strength (lbs) 91,200 11.06 85,10010.34 74,200 10.34 66,600 10.95 58,000 10.16 53,400 10.80

EXAMPLE 15 Dimensional Stability

The unannealed articles of EXAMPLE 8N were subject to x-ray diffractionanalysis, and displayed crystallinity levels of about 11 to 12 percentoverall. The majority of the crystallinity was assigned by x-raydiffraction techniques to the poly(p-dioxanone) phase. Once annealed,the molded parts had superior dimensional stability. The articles ofEXAMPLE 9 exhibited greater crystallinity levels than their EXAMPLE 8counterparts. Indeed, the annealed articles of EXAMPLE 9N were alsoanalyzed by x-ray diffraction and showed higher crystallinity levels ofabout 38 to 41 percent.

The molded articles of EXAMPLE 9 were tested for dimensional stability.The dimensions of the molded articles were measured prior to annealingand after annealing; additionally photographic images were taken.Although it is not expected to have dimensions match exactly, it isclear that unacceptable levels of distortion exist. In some cases,excessive distortion results in diminished functionality.

The test articles of EXAMPLE 9 are geometrically complex and have anumber of critical dimensions. For instance, if the legs of the moldedarticle distort excessively, the ability of the device to penetrate andhold tissue will be reduced. Likewise, if the barbs of the moldedarticle were to shrink significantly, functionality would be reducedbecause of diminished ability to hold tissue. Every design will have itsown critical dimensions. It is believed that the design of EXAMPLE 7 isrepresentative of a demanding device regarding dimensional stability;this is felt in part because of geometric complexity. Additionally, thefine part size will tend to increase molecular orientation duringinjection molding leading to an increased driving force for distortionof the ejected part at elevated temperatures as seen in annealing,and/or sterilization, and/or storage.

Parts were evaluated and characterized in a “pass/fail” manner.Disposition of the molded articles were based on gross warping effects,of which an article is considered to have passed if excessive distortionis not evident. Likewise, if excessive distortion is evident, the partis said to have failed. Inherently, all injection molded articles havesome degree of residual stress after molding, so parts that displaytolerable levels of distortion are said to have passed the dimensionalstability test.

For the articles of EXAMPLE 9, the tip-to-tip distance is a criticaldimension; see FIG. 3. FIG. 3 is a drawing of the device of FIG. 2showing the critical dimensions of said device. These dimensions, ifchanged by lack of dimensional stability, can lead to poor performanceand or failure of the device. A tip-to-tip distance of less than to0.115 inches for the articles of EXAMPLE 9 were said to be acceptable,while a tip-to-top distance greater than or equal to 0.115 inches weresaid to be unacceptable and denoted as “failure mode one” or “fm1”.Likewise, the length of the barb members from EXAMPLE 9 were alsoconsidered critical dimensions. A barb length of less than or equal to0.136 inches were considered unacceptable and denoted as “failure mode2” or “fm2”.

The photographic images and dimensions were captured using a Keyencedigital microscope, model VHX-600, with a magnification of 20×. The testresults are shown in Table IV.

TABLE IV Dimensional Stability Results on Injection Molded Articles ofEXAMPLES 8 and 9 made from the Lactide-Rich Lactide/Glycolide(Co)Polymer with Poly(p-dioxanone) Melt Blends of EXAMPLE 6 DimensionalBefore After Stability Grade/ Molded Device Annealing Annealing ReasonFor EXAMPLE No.* FIG. No. FIG. No. Failure** 8 and 9 A (0, 100) Failed:fm1, fm2 8 and 9 B (5, 100) Failed: fm1 8 and 9 C (7.5, 100) 6a 6bFailed: fm1 8 and 9 D (9, 100) 7a 7b Pass 8 and 9 E (10, 100) Pass 8 and9 F (24, 100) Pass 8 and 9 G (20, 95) Pass 8 and 9 H (9, 90) Failed:fm1, fm2 8 and 9 J (12, 90) Pass 8 and 9 K (15, 90) Pass 8 and 9 L (10,85) Failed: fm1 8 and 9 M (15, 85) Pass 8 and 9 N (20, 85) 8a 8b Pass 8and 9 P (13, 80) Failed: fm2 8 and 9 Q (17, 80) Pass 8 and 9 R (20, 80)Pass 8 and 9 S (15, 75) 9a 9b Failed: fm1 8 and 9 T (17.5, 75) 10a  10b Pass 8 and 9 W (20, 75) Pass 8 and 9 X (24, 75) 11a  11b  Pass *EXAMPLE8 refers to the molded articles prior to annealing, while EXAMPLE 9 isafter annealing **Key for Mode of Failure: fm1 = Increase in tip-to-tipdistance; fm2 = Shrinkage of one or both barbs

FIG. 6a is a photograph of an injection molded tack of EXAMPLE 8C (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6C thatprovided injection molded tacks exhibiting unacceptable warping afterannealing. FIG. 6b is a photograph of an injection molded tack ofEXAMPLE 9C (similar to the tack of FIG. 6a , but after annealing) madefrom the polymer composition of EXAMPLE 6C that provided injectionmolded tacks exhibiting unacceptable warping after annealing.

FIG. 7a is a photograph of an injection molded tack of EXAMPLE 8D (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6D thatprovided injection molded tacks that exhibit superior dimensionalstability and an acceptable level of warping after annealing. FIG. 7b isa photograph of an injection molded tack of EXAMPLE 9D (similar to thetack of FIG. 7a , but after annealing) made from the polymer compositionof EXAMPLE 6D that provided injection molded tacks that exhibitedsuperior dimensional stability and an acceptable level of warping afterannealing.

FIG. 8a is a photograph of an injection molded tack of EXAMPLE 8N (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6N thatprovided injection molded tacks that exhibited superior dimensionalstability and an acceptable level of warping after annealing. FIG. 8b isa photograph of an injection molded tack of EXAMPLE 9N (similar to thetack of FIG. 8a , but after annealing) made from the polymer compositionof EXAMPLE 6N that provided injection molded articles that exhibitedsuperior dimensional stability and an acceptable level of warping afterannealing.

FIG. 9a is a photograph of an injection molded tack of EXAMPLE 8S (i.e.,prior to annealing) made from the polymer composition of EXAMPLE 6S thatprovided injection molded tacks that exhibited unacceptable warpingafter annealing. FIG. 9b is a photograph of an injection molded tack ofEXAMPLE 9S (similar to the tack of FIG. 9a , but after annealing) madefrom the polymer composition of EXAMPLE 6S, that provided injectionmolded tacks that exhibited unacceptable warping after annealing.

FIG. 10a is a photograph of an injection molded tack of EXAMPLE 8T(i.e., prior to annealing) made from the polymer composition of EXAMPLE6T that provided injection molded tacks that exhibited superiordimensional stability and an acceptable level of warping afterannealing. FIG. 10b is a photograph of an injection molded tack ofEXAMPLE 9T (similar to the tack of FIG. 10a , but after annealing) madefrom the polymer composition of EXAMPLE 6T that provided injectionmolded tacks that exhibited superior dimensional stability and anacceptable level of warping after annealing.

FIG. 11a is a photograph of an injection molded tack of EXAMPLE 8X(i.e., prior to annealing) made from the polymer composition of EXAMPLE6X that provided injection molded tacks that exhibited superiordimensional stability and an acceptable level of warping afterannealing. FIG. 11b is a photograph of an injection molded tack ofEXAMPLE 9X (similar to the tack of FIG. 11a , but after annealing) madefrom the polymer composition of EXAMPLE 6X that provided injectionmolded tacks that exhibited superior dimensional stability and anacceptable level of warping after annealing.

EXAMPLE 16 Absorption Profile

The articles of the present invention are absorbable in bodily tissue.In general, the greater the amount of glycolide in the lactide-richpoly(lactide-co-glycolide) copolymer, the faster the article willabsorb. Additionally, the greater the amount of poly(p-dioxanone) in thepolymer blend, the faster the article will absorb.

Annealed injection molded articles substantially similar in design toFIG. 2 made from polymer blends of lactide-richpoly(lactide-co-glycolide) and poly(p-dioxanone) were tested forhydrolysis time at a pH of 7.27 and a temperature of 70° C. The data inTable V summarizes the results of this accelerated hydrolysis test.

TABLE V Accelerated Hydrolysis Values Mol Percent of Polymerized Lactidein Weight Percent the Lactide-Based Poly(p-dioxanone) Time for Complete(Co)Polymer Polymer in the Blend Hydrolysis (Hours) 90 20 360 85 30 26080 20 220 80 30 200

EXAMPLE 17 Determination of Blend Morphology

A determination was made of the morphology of the minor component of theinjection molded articles from the polymer blend of 20 weight percentpoly(p-dioxanone) and 80 weight percent poly(lactide-co-glycolide),wherein the poly(lactide-co-lactide) is 85 mol percent lactide and 15mol percent glycolide. The photomicrograph was obtained according to thefollowing procedure: an injection molded device was cut into 8 smallpieces to expose all internal structures; the small pieces were immersedin chloroform (5 ml) overnight to dissolve thepoly(lactide-co-glycolide) component of the blend. The chloroformsolution then was shaken to break the entangled fibrous structure; thesolution then was passed through a polypropylene filter with a pore sizeof 0.3 μm; the filter was then rinsed with chloroform to remove anypossible lactide/glycolide copolymer deposited on the filter; thepoly(p-dioxanone) structures left on the filter surface then werestudied with SEM.

FIG. 1 is an SEM photomicrograph of the collected poly(p-dioxanone)structures of the injection molded articles from the polymer blend of 20weight percent poly(p-dioxanone) and 80 weight percentpoly(lactide-co-glycolide), wherein the poly(lactide-co-lactide) is 85mol percent lactide and 15 mol percent glycolide. The aspect ratio ofthe poly(p-dioxanone) phase is well above one indicating a high level ofshear during the fabrication process which typically leads to highresidual stress levels increasing the driving force for subsequentshrinkage and warpage.

EXAMPLE 18 Applicability of Inventive Blend for Medical Devices

It is to be understood that the blend of the present invention can beused to fabricate medical devices using various melt processingtechniques. As shown in some of the above examples, injection molding isone of the techniques that is applicable. It is further understood thata variety of designs may be employed utilizing the inventive blends.

One such device that was produced was in the form of a dumbbell 0.35inches in length with substantially disk-like termini 0.20 inches indiameter and 0.05 inches in thickness. The connection between the twodisks had a substantially circular cross-section, 0.062 inches indiameter. FIG. 12 provides engineering drawings of this dumbbell device.This design was injection molded using a 90/10 lactide/glycolidecopolymer as a control and a polymer blend of the present invention,specifically a melt blend of 20 weight percent poly(p-dioxanone) and 80weight percent 90/10 lactide/glycolide copolymer. The articles, soproduced, were thermally annealed without restraint at 60, 70, and 80 Cfor 8, 4 and 4 hours, respectively. The devices molded from the 90/10lactide/glycolide copolymer showed substantial shrinkage and warpageafter this annealing process. The devices molded from the inventiveblend were substantially free of shrinkage and warpage after annealing.

It is expected that the blends of the present invention would be usefulin fabricating, via injection molding, a very wide array of devicesincluding, but not limited to staples, pins, screws, plates, clips,anchors, tissue engineering scaffolds, and wound closure devices. Inaddition it is also expected that other processing methods might beemployed to form useful articles using the present inventive blends.These processes include, but are not limited to, fiber extrusion,profile extrusion, film extrusion, tube extrusion, and blow molding. Oneskilled in the art could for instance cut or punch specific shapes tofabricate devices from sheet stock formed from extrusion methodologies.It will be evident to one skilled in the art to select an appropriateforming methodology.

EXAMPLE 19 Melt Blending During Fabrication of the Medical Device

As mentioned earlier, an alternate method of forming the melt blend ofthe present invention was to add the appropriately sized blendcomponents directly to the hopper of the injection molding machine. Themelt blending occurred within the confines of the injection moldingmachine's barrel producing acceptable parts as described in EXAMPLE 7.

EXAMPLE 20 Calculating the Minimum Weight Percent of Poly(p-dioxanone)in the Invention

As stated previously, the minimum level of poly(p-dioxanone) wasdependent on the molar amount of polymerized lactide present in thelactide-based polymer present in the blend and was calculated using theequation found below.Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027)

For example, when the composition of the lactide-co-glycolide copolymerwas 82/8 (on a mol basis), the minimum weight percent ofpoly(p-dioxanone) in the blend was calculated to be 10 percent and themaximum amount was approximately 24. Likewise, if the composition of thelactide-co-glycolide copolymer was 86/14 (on a mol basis), the minimumweight percent of poly(p-dioxanone) in the blend was calculated to be 12percent and the maximum amount was approximately 24. Table VI contains achart of the range of poly(p-dioxanone), expressed as minimum andmaximum weight percent, in the blend of the subject invention.

TABLE VI Inventive Blend Compositions of Lactide-Rich, Lactide/Glycolide(Co)Polymer with Poly(p-dioxanone) Mol Percent of Minimum MaximumPolymerized Lactide Weight Percent Weight Percent in the Lactide-BasedPoly(p-dioxanone) Poly(p-dioxanone) (Co)Polymer Polymer in the BlendPolymer in the Blend 100 8.0 Approximately 24 99 8.2 Approximately 24 988.4 Approximately 24 97 8.7 Approximately 24 96 8.9 Approximately 24 959.2 Approximately 24 94 9.4 Approximately 24 93 9.7 Approximately 24 9210.0 Approximately 24 91 10.3 Approximately 24 90 10.6 Approximately 2489 10.9 Approximately 24 88 11.3 Approximately 24 87 11.6 Approximately24 86 12.0 Approximately 24 85 12.4 Approximately 24 84 12.8Approximately 24 83 13.2 Approximately 24 82 13.6 Approximately 24 8114.1 Approximately 24 80 14.6 Approximately 24 79 15.1 Approximately 2478 15.6 Approximately 24 77 16.2 Approximately 24 76 16.7 Approximately24 75 17.4 Approximately 24 74 18.0 Approximately 24 73 18.7Approximately 24 72 19.4 Approximately 24 71 20.1 Approximately 24 7020.9 Approximately 24

FIG. 5 is a graph of mol percent lactide in the lactide/glycolidecopolymer component versus weight percent of poly(p-dioxanone); the areabounded by the curves shows the novel polymer compositions of thepresent invention.

Although this invention has been shown and described with respect todetailed embodiments thereof, it will be understood by those skilled inthe art that various changes in form and detail thereof may be madewithout departing from the spirit and scope of the claimed invention.

We claim:
 1. A bioabsorbable melt polymer blend, comprising: 82 weightpercent to 88 weight percent of a first bioabsorbable polymer and 12weight percent to 18 weight percent of a second bioabsorbable polymer,the first bioabsorbable polymer comprising a lactide-rich polymercomprising about 95 mol percent to about 75 mol percent polymerizedlactide and about 5 mol percent to about 25 mol percent polymerizedglycolide, and the second bioabsorbable polymer comprisingpoly(p-dioxanone), wherein the polymer blend has a maximum weightpercent of poly(p-dioxanone) of 18 weight percent and a minimum weightpercent of poly(p-dioxanone) that depends upon the molar amount ofpolymerized lactide in the lactide-rich polymer and is calculated by theexpression:Weight Percent Poly(p-dioxanone)=(215.6212/Mol Percent PolymerizedLactide)^(2.7027) and wherein the polymer blend provides dimensionalstability to a manufactured article.